A Novel Fibrinolytic Enzyme (Nattokinase) in the Vegetable Cheese Natto: A Typical Soybean Food Made from Fermented Soybeans

This 1987 paper describes the discovery and initial characterization of nattokinase — a serine protease isolated from natto (fermented soybeans) — demonstrating fibrinolytic activity in vitro comparable to plasmin, the body’s primary fibrinolytic enzyme. Nattokinase was found to dissolve fibrin clots in vitro at rates comparable to urokinase, with stability across a range of pH and temperature conditions.

The initial discovery paper establishes the existence of a fibrinolytically active enzyme in a traditional Japanese fermented food. The fibrinolytic capacity observed in vitro launched subsequent research into whether oral nattokinase retains activity after intestinal transit and whether it can modify thrombus formation or fibrinolysis in vivo.

This paper is the foundational reference for the nattokinase literature — cited in virtually all subsequent studies of the compound. Its clinical relevance to coronary artery disease is indirect: nattokinase does not substantially reduce LDL-C, ApoB, or Lp(a), and has not been evaluated in randomized trials for cardiovascular endpoints. The mechanistic hypothesis — oral fibrinolytic supplementation to reduce coronary thrombosis risk — lacks the pharmacokinetic and clinical outcome evidence that would make it clinically actionable.

We rate the evidence limited. A discovery-level basic science paper identifying nattokinase’s in vitro fibrinolytic properties — foundational for the nattokinase literature but far upstream from clinical cardiovascular outcome evidence.